GB885981A - New reserpine analogues and process for their manufacture - Google Patents

Abstract

The invention comprises 17-lower alkoxy-18-hydroxy-3-epialloyohimbane-16-carboxylic acid esters etherified in 18-position with an alcohol of aliphatic character and with the nucleus of formula <FORM:0885981/IV (b)/1> in which the substituents at 16-, 17- and 18-have the same configuration as in d- or l-reserpine, their N-oxides and salts of these compounds, with the proviso that in reserpic acid esters etherified in the 18-position the ether radical bound to the 18-carbon atom and the alcohol radical of the ester contain together more than two carbon atoms, and a process for their preparation by reacting the corresponding 18-hydroxy compound or an N-oxide or salt thereof with a diazo compound of aliphatic character in the presence of a strong inorganic Lewis acid, and, if necessary, converting a resulting tertiary amine into an N-oxide, a resulting base into a salt, an N-oxide into the corresponding amine, or a salt into the corresponding base. The preferred compounds are of the general formula <FORM:0885981/IV (b)/2> in which R1 is an unsubstituted or substituted lower alkyl group, R2 is lower alkyl, R3 is an unsubstituted or substituted hydrocarbon radical of aliphatic character, R4 and R5 each are hydrogen or halo atoms or lower aliphatic hydrocarbon radicals, etherified or esterified hydroxyl groups, etherified mercapto, nitro, or amino groups, halo-lower alkyl radicals, or together (in adjacent positions) from a cyclic substituent, e.g. methylene-dioxy, R6 in one of positions 5 or 6 stands for hydrogen or an alkyl radical, and salts of these compounds. Specific examples of the R3 radical are lower alkyl, lower alkenyl, cycloalkyl, cycloalkenyl, cycloalkyl-lower alkyl, aryl-lower alkyl, aryl-lower alkenyl, in which the lower alkyl groups may be further substituted by alkoxy, mercapto, amino, acyl groups or halogen atoms and the aryl radicals may be further substituted by lower alkyl, lower alkoxy, lower alkenyloxy, halogen, lower alkoxy carbonyloxy, halogen lower alkyl, nitro or amino groups. Detailed examples are given and many compounds are also tabulated. n-Propyl reserpate is prepared by treating reserpic acid with n-diazopropane. Isopropyl, isobutyl and n-hexyl reserpates are likewise prepared from the appropriate diazo alkanes.ALSO:In preparing feeds, for poultry and other animals, containing corn meal, fat, mineral salts such as manganese sulphate, di-calcium carbonate and iodized salt, fish meal, soybean meal, corn gluten meal, corn distillers' solubles and vitamins &c., a portion of the corn meal previously blended with the pre-heated, liquefied fat is added to the remainder of the corn meal in a blending machine, thereafter the mineral salts, fish meal, soybean meal, corn gluten meal and corn distillers' solubles are added in turn and after a uniform mixture has been obtained, vitamins A and D, calcium pantothenate, choline chloride, riboflavin, Vitamin B12 and methionine are added in that order; butylated hydroxy toluene is added and mixing is continued until a uniform product is obtained. The feed may include also dehydrated alfalfa meal. The relative proportions of the ingredients are disclosed.ALSO:Pharmaceutical compositions having a hypotensive action comprise 17-lower alkoxy-18-hydroxy - 3 - epi - alloyohimbane - 16 - carboxylic esters etherified in 18-position with an alcohol of aliphatic character and with a nucleus of the formula <FORM:0885981/VI/1> (in which the substituents in 16-, 17- and 18-position have the same configuration as in d- or l-reserpine, their N-oxides and salts of these compounds, with the proviso that in the reserpic esters etherified at C18 the ether radical bound to the 18-O-atom and the alcohol radical of the ester group together contain more than two carbon atoms) together with a pharmaceutical carrier suitable for oral or parenteral use. The compositions may take the form of tablets, solutions or elixirs. Examples detail the formulation of ethyl 18-O-methyl reserpate in tablets. Specified salts are hydrohalides, sulphates, phosphates, acetates, propionates, glycollates, lactates, pyruvates, oxalates, malonates, succinates, maleates, fumarates, malates, tartrates, citrates, ascorbates, citraconates, mono- and dihydroxymaleates, benzoates, phenylacetates, 4-aminobenzoates, 4 - hydroxybenzoates, anthranilates, cinnamates, mandelates, salicylates, 4 - aminosalicylates, 2 - phenoxybenzoates, 2 - acetoxybenzoates and methane-, ethane, 2 - hydroxyethane - and p - toluene-sulphonates.